This invention relates to a process for the preparation of 3,5-diaminobenzotrifluoride by the reduction of 4-chloro-3,5-dinitrobenzotrifluoride using hydrogen as a reducing agent in the presence of palladium on charcoal as a catalyst. 3,5-Diaminobenzotrifluoride is a valuable intermediate for use in the synthesis of polyimide polymers.
The reduction of aromatic nitro compounds containing halogen on the aromatic ring is unpredictable. Hydrogenation using a palladium on charcoal catalyst generally reduces the nitro group to an amine. However, the hydrogenation has been reported to fail in some cases. In addition, the effects of such hydrogenation upon a ring halogen are unpredictable. Occasionally the ring halogen is removed from the ring and replaced by a hydrogen. However, in many cases the hydrogenation leaves the ring halogen intact.
A. Weizmann discloses in J. Am. Chem. Soc., 71, 4154 (1949), that the catalytic hydrogenation of diethylaminoethyl-4-nitro-2-chlorobenzoate using palladium on barium sulfate as a catalyst was impractical from a preparative point of view. The nitro compound was often incompletely reduced. The chlorine was occasionally removed from the ring while in other reactions it remained on the ring. Similar hydrogenation experiments conducted with 2-chloro-4-nitrobenzoic acid and its ethyl ester, using palladium on barium sulfate as a catalyst, produced variable results depending upon the solvent employed. In ethyl acetate, the reduction proceeded with retention of the chlorine, and the acid and the ethyl ester gave quantitative yields of 4-amino-2-chlorobenzoic acid and ethyl 4-amino-2-chlorobenzoate, respectively. In other words, the use of ethyl acetate as a solvent caused reduction without removal of the chlorine attached to the ring. In isopropyl alcohol, the 2-chloro-4-nitrobenzoic acid and its ethyl ester were reduced to 4-aminobenzoic acid and its ethyl ester respectively. In other words, the chlorine was lost in the reduction process. An aqueous solution of sodium 2-chloro-4-nitrobenzoate yielded, on workup, 4-aminobenzoic acid.
Bouchet et al. disclose in Syn. Commun., 4, 57-9 1974) that para-nitrochlorobenzene may be reduced to para-chloroaniline using hydrogen in the presence of a palladium on carbon catalyst.
Ovchinnikov, et al. (in Z. Prikl. Khim., (62), 37-44 (1969)) that meta- and para-chloronitrobenzenes may be hydrogenated to meta- and para-chloroanilines respectively using hydrogen gas and a 2% palladium on carbon catalyst. Approximately 2% dehalogenation was observed. It was also observed that the amount of dehalogenation was related to the type of carbon used as the catalyst carrier as well as the height of the catalyst bed.
U.S. Pat. No. 4,022,795 discloses a process for dehalogenating aromatic compounds using a formic acid salt and a hydrogenation catalyst. If a nitro group is present in the aromatic molecule, it may be reduced in the process. Under certain conditions, internuclear bonds are formed and thus, a chlorobenzene may yield a biphenyl derivative.
U.S. Pat. No. 3,666,813 discloses that aromatic haloamines may be prepared by hydrogenating the corresponding chloro-nitro aromatic compound in the presence of a modified palladium on charcoal catalyst. The palladium on carbon catalyst is modified by treating it with a solution of a bismuth, lead or silver salt.
European Pat. Application EP 88667 (as abstracted in Chem. Abstracts 100:52475m and Derwent accession #C83-089930) discloses that chlorinated or brominated methylenedianilines may be prepared by the nitration and reduction of the corresponding aromatic halides. The reduction is carried out in methanol solvent with hydrogen gas in the presence of 5% palladium on carbon as a catalyst. The halogen is not removed in this process.
European Pat. Application EP-38465 teaches the reduction of 2-trifluoromethyl-4-chloronitrobenzene to 2-trifluoromethylaniline in a single step using hydrogen gas in a polar medium. The preferred solvent is water and/or a 1-3 carbon alcohol, especially methanol, and the preferred bases are alkali hydroxides, ammonia, or lower aliphatic amines.
Chakrabarti et al. disclose in two papers (J. Med. Chem. 23, p. 878 and 884 (1980)) a multi-step reduction reaction in which the first step is hydrogenation using 10% palladium on carbon as a catalyst. The molecules that are subjected to hydrogenation are substituted nitrobenzenes with a halogen at the 3-position and a substituted amino group at the 6-position. In one paper the compound studied has fluorine as the halogen and in the other the halogen is chlorine. In each case, the nitro group was reduced to the amine while the halogen was not attacked.
Japanese Pat. No. 63/010739 (as abstracted in Chem. Abstracts 109:92449y) discloses that chloro-fluoro-benzotrifluoride derivatives can be dechlorinated using hydrogen gas and 5% palladium charcoal catalysts in a methanol solvent. The ring chlorines are preferentially removed over the ring fluorines.
Vergnani et al. disclose in Helv. Chim. Acta, 68, 1828, (1985), that 5-bromo-2-methyl-8-nitro-1,2,3,4-tetrahydroisoquinoline undergoes simultaneous removal of the aromatic bromine and reduction of the nitro group to an amine when treated with hydrogen gas in the presence of a 10% palladium on charcoal catalyst, triethyl amine and methanol as a solvent.
Japanese Pat. No. 58157749 (as abstracted in Chem. Abstracts 100:51247b) discloses that 2,2',4-trichloro-4',5-dinitrodiphenyl ether may be hydrogenated in the presence of 5% palladium on carbon catalyst in methanol to form 5 3,4'-diaminodiphenyl ether.
Crampton and Greenhalgh have disclosed, in J. Chem. Soc., Perkin Transaction II, p. 187 (1986), that 4-chloro-3,5-dinitrobenzotrifluoride is subject to nucleophilic attack at the carbon-chlorine bond. Thus, hydroxide ion can displace the chlorine to yield 4-hydroxy-3,5-dinitro benzotrifluoride. The substance that is reduced using the process of this invention, that is, 4-chloro-3,5-dinitro benzotrifluoride, is a rather reactive molecule and can undergo side reactions during any reduction process.
Attempts were made in our laboratories to reduce 4-chloro-3,5-dinitro benzotrifluoride using sodium formate and a palladium on carbon catalyst. A variety of dipolar aprotic solvents and methanol were used. In all cases the reduction was either incomplete or did not occur at all, and the products formed indicated that the 4-chloro group had been displaced to form either 4-hydroxy compounds or, in the case of methanol, a 4-methoxy compound. (See Comparative Examples 1-4.) Attempts were also made to use sodium formate as a base. The reaction product was a mixture of the desired 3,5-diaminobenzotrifluoride and the undesirable 4-chloro-3,5-diaminobenzotrifluoride. (See Comparative Example 8)